This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mitochondria are the organelles responsible for oxidative phosphorylation. The efficiency and regulation of oxidative metabolism is critical to sustain different physiological processes. Mitochondrial deficiencies that affect oxidative metabolism are linked to aging, neurodegeneration and a variety of genetic mitochondrial diseases. Mitochondrial function is strictly dependent on the expression of the mitochondrial genome, and mitochondrial gene transcription is a key link in this process. Our laboratory is currently trying to understand the structural biology and biochemistry of the mitochondrial transcription machinery and to study its control by nuclear hormone receptors. Elucidating the mechanisms of regulation of this key cellular process has important implications for a number of human diseases and may lead to new potential avenues for therapeutics.